Dystonia and Cerebellum : From Bench to Bedside

Dystonia pathogenesis remains unclear; however, findings from basic and clinical research suggest the importance of the interaction between the basal ganglia and cerebellum. After the discovery of disynaptic pathways between the two, much attention has been paid to the cerebellum. Basic research using various dystonia rodent models and clinical studies in dystonia patients continues to provide new pieces of knowledge regarding the role of the cerebellum in dystonia genesis. Herein, we review basic and clinical articles related to dystonia focusing on the cerebellum, and clarify the current understanding of the role of the cerebellum in dystonia pathogenesis. Given the recent evidence providing new hypotheses regarding dystonia pathogenesis, we discuss how the current evidence answers the unsolved clinical questions

Effect of a Rehabilitation Program After Mesenchymal Stromal Cell Transplantation for Advanced Osteonecrosis of the Femoral Head: A 10-Year Follow-Up Study

Objective: To assess the status of 10 patients with advanced osteonecrosis of the femoral head who underwent mesenchymal stromal cell transplants and a 12-week rehabilitation program 10 years earlier. Design: Retrospective study. Setting: University clinical research laboratory. Participants: Patients (N=10) who had undergone mesenchymal stromal cell transplantation and rehabilitation for a single hip osteonecrosis of the femoral head 10 years prior to the current study were recruited by telephone. The average age was 31.7 years and all participants were men; radiographic stages were 3A in 6 patients and 3B in 4 patients before treatment. Intervention: A 12-week rehabilitation program with follow-up once every 1 to 2 years was performed after mesenchymal stromal cell transplantation. Main Outcome Measures: Radiographic analysis, clinical score, timed Up and Go test, hip function (range of motion, muscle strength), and Short Form-36 scores were assessed before treatment and 1 and 10 years after treatment. Results: Upon imaging, 5 hips were found to be stable (stable group) and 5 had progressed (progressed group); 2 of the latter group required a total hip arthroplasty. The pretreatment radiographic stage of the progressed group was more advanced than that of the stable group. Body mass index was higher in the progressed group than in the stable group. Hip function and clinical score at 1 and 10 years after treatment improved in the hips of 8 patients without total hip arthroplasty. There were no severe adverse events during the rehabilitation. Conclusions: The 12-week rehabilitation program and annual follow-up after mesenchymal stromal cell transplantation for osteonecrosis of the femoral head was associated with pain reduction, maintaining hip muscle strength, widening range of motion, and improving quality of life. The level and timing of weight-bearing and social activity should be planned according to the individual's lifestyle and body composition

L-Qモデルは転移性脳腫瘍の定位放射線照射に適用可能か?

The biologically effective dose (BED) based on the linear-quadratic (LQ) model has been commonly used to evaluate the dose-effect relationships among the different fractionation schedules, but whether the LQ model is appropriate for hypofractionated (HF) high-dose stereotactic irradiation (STI) is uncertain. The validity of the model at high doses per fraction has been critically examined. In this study, STI of metastatic brain tumors was evaluated to suggest the applicability of the LQ model to HF high-dose radiotherapy. No significant difference was found between stereotactic radiosurgery (SRS) and HF stereotactic radiotherapy (SRT) in the analyses of 151 tumors. Furthermore, no significant differences were found among SRS, HF-SRT, and non-HF SRT in 117 metastatic lung adenocarcinomas. The results of this study suggest that BED calculation is a reasonable approach for careful dose-effect evaluation based on the LQ model for HF high-dose radiotherapy for metastatic brain tumors, especially lung adenocarcinomas.博士（医学）・甲第688号・平成30年9月26

A First View of the Effect of a Trial of Early Mobilization on the Muscle Strength and Activities of Daily Living in Mechanically Ventilated Patients With COVID-19

Objective: To retrospectively investigate the effect of early mobilization on the muscle strength and activities of daily living in patients with COVID-19 under mechanical ventilation. Design: This was a single-center, retrospective, observational study. Setting: Inpatient rehabilitation care in Japan. Participants: The study subjects were divided based on the onset of mobilization: under mechanical ventilation (n=17; aged 68.5±11.9, 13 male) and after extubation (n=11; aged 59.7±7.1, 6 male; N=28). Interventions: Mobilization, including dangle sitting, standing, walking, and muscle strengthening exercises. Main Outcome Measures: The outcome measures were Barthel Index, Medical Research Council Manual Muscle Test, and intensive care unit Mobility Scale. Results: The difference in the Barthel Index, Medical Research Council Manual Muscle Test, and intensive care unit Mobility Scale scores pre- and postintervention were not statistically significant between the 2 groups, but all significantly improved after the intervention. Conclusion: This small sample size study found no difference in the functional recovery of patients with severe COVID-19 who underwent early mobilization under mechanical ventilation relative to when it was begun after extubation

Large-scale Filamentary Structure around the Protocluster at Redshift z=3.1

We report the discovery of a large-scale coherent filamentary structure of Lyman alpha emitters in a redshift space at z=3.1. We carried out spectroscopic observations to map the three dimensional structure of the belt-like feature of the Lyman alpha emitters discovered by our previous narrow-band imaging observations centered on the protocluster at z=3.1. The feature was found to consist of at least three physical filaments connecting with each other. The result is in qualitative agreement with the prediction of the 'biased' galaxy-formation theories that galaxies preferentially formed in large-scale filamentary or sheet-like mass overdensities in the early Universe. We also found that the two known giant Lyman alpha emission-line nebulae showing high star-formation activities are located near the intersection of these filaments, which presumably evolves into a massive cluster of galaxies in the local Universe. This may suggest that massive galaxy formation occurs at the characteristic place in the surrounding large-scale structure at high redshift.Comment: 11 pages, 3 figures, accepted for publication in ApJ Letter

脳幹部転移性脳腫瘍に対する寡分割定位放射線治療の治療成績

Background: To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. Methods: Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n = 18, 75.0%), colon (n = 3, 12.5%), and breast (n = 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. Results: Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. Conclusions: Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.博士（医学）・乙第1450号・令和2年3月16日Copyright © 2019 Elsevier Inc. All rights reserved